TY - JOUR
T1 - Induction of a long noncoding rn A Transcript, NR-045064, promotes defense gene transcription and facilitates intestinal epithelial cell responses against cryptosporidium infection
AU - Li, Min
AU - Gong, Ai Yu
AU - Zhang, Xin Tian
AU - Wang, Yang
AU - Mathy, Nicholas W.
AU - Martins, Gislaine A.
AU - Strauss-Soukup, Juliane K.
AU - Chen, Xian Ming
N1 - Funding Information:
This work was supported by the National Institutes of Health (AI116323 and AI136877) and the Nebraska Cancer and Smoking Disease Research Program (LB595) to X.-M.C. and by Grant G20RR024001 from the National Center for Research Resources.
Publisher Copyright:
©2018 by The American Association of Immunologists,Inc.
PY - 2018/12/15
Y1 - 2018/12/15
N2 - Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding rn A (lncrn A) expression profiles in murine intestinal epithelial cells. Transcription of a panel of lncrn A genes, including NR045064, in infected cells is controlled by the NF-kB signaling. Functionally, inhibition of NR045064 induction increases parasite burden in intestinal epithelial cells. Induction of NR045064 enhances the transcription of selected defense genes in host cells following C. parvum infection. Epigenetic histone modifications are involved in NR045064-mediated transcription of associated defense genes in infected host cells. Moreover, the p300/MLL-associated chromatin remodeling is involved in NR045064-mediated transcription of associated defense genes in intestinal epithelial cells following C. parvum infection. Expression of NR045064 and associated genes is also identified in intestinal epithelium in C57BL/6J mice following phosphorothioate oligodeoxynucleotide or LPS stimulation. Our data demonstrate that lncrn As, such as NR045064, play a role in regulating epithelial defense against microbial infection. The Journ Al of Immunology, 2018, 201: 3630-3640.
AB - Cryptosporidium is an important opportunistic intestinal pathogen for immunocompromised individuals and a common cause of diarrhea in young children in developing countries. Gastrointestinal epithelial cells play a central role in activating and orchestrating host immune responses against Cryptosporidium infection, but underlying molecular mechanisms are not fully understood. We report in this paper that C. parvum infection causes significant alterations in long noncoding rn A (lncrn A) expression profiles in murine intestinal epithelial cells. Transcription of a panel of lncrn A genes, including NR045064, in infected cells is controlled by the NF-kB signaling. Functionally, inhibition of NR045064 induction increases parasite burden in intestinal epithelial cells. Induction of NR045064 enhances the transcription of selected defense genes in host cells following C. parvum infection. Epigenetic histone modifications are involved in NR045064-mediated transcription of associated defense genes in infected host cells. Moreover, the p300/MLL-associated chromatin remodeling is involved in NR045064-mediated transcription of associated defense genes in intestinal epithelial cells following C. parvum infection. Expression of NR045064 and associated genes is also identified in intestinal epithelium in C57BL/6J mice following phosphorothioate oligodeoxynucleotide or LPS stimulation. Our data demonstrate that lncrn As, such as NR045064, play a role in regulating epithelial defense against microbial infection. The Journ Al of Immunology, 2018, 201: 3630-3640.
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U2 - 10.4049/jimmunol.1800566
DO - 10.4049/jimmunol.1800566
M3 - Article
C2 - 30446564
AN - SCOPUS:85058393994
VL - 201
SP - 3630
EP - 3640
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -